Fate of pesticides in soil in a coastal lagoon area and associated water quality impacts.
Pesticides used on agricultural lands are among the significant diffuse sources of pollutants. They are poisons and can be particularly dangerous when misused and/or applied without care. Although certain characteristics of pesticides are well known, their final characteristics after they reach a waterbody are extremely difficult to estimate. Regarding the soil and water environment, it is necessary to conduct both a field study and laboratory analysis. Such a study has been performed in the catchment area of Dalyan Lagoon, Turkey, joining the Mediterranean Sea, that was selected as the pilot region. The input of pesticides, transport in soil and transfer to the water environment together with their probable impacts on water quality are determined by conducting detailed field surveys and water residue analyses. Within the scope of the study, the behavior and fate of pesticides both in soil and water are investigated in detail. Water residue experiments are conducted on four sets of water samples representing the seasons of the year 1999-2000 for the pre-selected 6 pesticides. Two sets of water samples (surface and bottom) are taken from the 16 stations along the lagoon channel and two lakes within the catchment area. The results and findings show the significance of the use of pesticides as they exist in the water environment around and/or slightly above the limits stated in the national current regulations except dichlorvos which presents very high values compared to its tolerance limit. Of particular interest, the results are used to enlighten the farmers and the public and increase awareness of pesticides as contaminants in valuable coastal waters.


A Simple Route toward Next-Generation Thiobase-Based Photosensitizers for Cancer Theranostics.
Sulfur-substituted biocompatible carbonyl fluorophores have been recognized as effective heavy-atom-free photosensitizers (PSs) for cancer therapy due to their remarkable phototherapeutic properties. However, guidelines on their molecular design are still a substantial challenge. Most of the existing thiocarbonyl-based PSs are nonemissive in both the solution and restricted states, which hinders their further biomedical applications. Herein, we report the interesting finding that sulfur-substituted coumarins exhibit an uncommon phenomenon, aggregation-induced emission. More intriguingly, we also found that the introduction of a strong electron-accepting trifluoromethyl group is crucial to facilitate the mitochondrial-targeting ability of neutral coumarin fluorophores. The resulting CMS-2 PS displayed selective imaging of mitochondria and exhibited much higher photodynamic therapy efficiency toward cancer cells than that of the commercial PS erythrosine B. This work provides deep insight into the molecular design of heavy-atom-free thiobase-based PSs and simultaneously offers a great opportunity to develop novel mitochondrial-targeting fluorescent indicators with neutral bioinspired platforms.


When is a choice not a choice? Pigeons fail to inhibit incorrect responses on a go/no-go midsession reversal task.
In a 2-stimulus visual discrimination choice task with a reversal in reward contingencies midway through each session, pigeons produce a surprising number of both anticipatory errors (i.e., responding to the second-correct stimulus before the reversal) and perseverative errors (i.e., responding to the first-correct stimulus after the reversal). Here, we used a go/no-go version of the task to examine the degree to which these errors can be attributed to failure to inhibit incorrect responses near the reversal. We presented pigeons with either a green or red stimulus (randomized across trials), with pecks to 1 reinforced with food and pecks to the other stimulus leading to a 10-s time-out; the reward versus time-out contingencies reversed after 40 trials. Pigeons rarely withheld responses when reward was provided for pecking, but produced many incorrect pecks near the reversal. Subsequent experiments examined these errors with longer sessions and multiple reversals, as well as on choice tasks. Our results suggest that pigeons' errors may be due to an inability to inhibit incorrect responses rather than a deliberate choice of the incorrect stimulus on simultaneous discrimination midsession reversal procedures. Results suggest that pigeons learned independent rules about the 2 stimuli, and that training with multiple reversals changed the rules that governed pigeons' responding. (PsycINFO Database Record


Cell lines from kidney proximal tubules of a patient with Lowe syndrome lack OCRL inositol polyphosphate 5-phosphatase and accumulate phosphatidylinositol 4,5-bisphosphate.
The protein product of the gene that when mutated is responsible for Lowe syndrome, or oculocerebrorenal syndrome (OCRL), is an inositol polyphosphate 5-phosphatase. It has a marked preference for phosphatidylinositol 4,5-bisphosphate although it hydrolyzes all four of the known inositol polyphosphate 5-phosphatase substrates: inositol 1,4,5-trisphosphate, inositol 1,3,4,5-tetrakisphosphate, phosphatidylinositol 4,5-bisphosphate, and phosphatidylinositol 3,4,5-trisphosphate. The enzyme activity of this protein is determined by a region of 672 out of a total of 970 amino acids that is homologous to inositol polyphosphate 5-phosphatase II. Cell lines from kidney proximal tubules of a patient with Lowe syndrome and a normal individual were used to study the function of OCRL. The cells from the Lowe syndrome patient lack OCRL protein. OCRL is the major phosphatidylinositol 4,5-bisphosphate 5-phosphatase in these cells. As a result, these cells accumulate phosphatidylinositol 4,5-bisphosphate even though at least four other inositol polyphosphate 5-phosphatase isozymes are present in these cells. OCRL is associated with lysosomal membranes in control proximal tubule cell lines suggesting that OCRL may function in lysosomal membrane trafficking by regulating the specific pool of phosphatidylinositol 4,5-bisphosphate that is associated with lysosomes.


Inverse association between dietary vitamin D and risk of cutaneous melanoma in a northern Italy population.
The possibility of an inverse association between vitamin D and risk of cancer and, in particular, of cutaneous malignant melanoma has been suggested, but results of epidemiologic studies are still conflicting. We examined the relation between dietary vitamin D intake and melanoma risk through a population-based case-control study (380 cases, 719 controls) in a northern region of Italy, a country with an average vitamin D intake lower than that in northern Europe or the United States. We assessed average daily intake of vitamin D from foodstuffs using the European Prospective Investigation into Cancer and Nutrition (EPIC) semiquantitative food frequency questionnaire. In this population, levels of vitamin D intake were considerably lower than those observed in recent U.S. studies. We found an inverse relation between dietary vitamin D and melanoma risk in the sample as a whole, in both crude and adjusted analyses. In sex- and age-specific analyses, this association appeared to be stronger among males and among older subjects. These findings suggest that, at the relatively low levels of intake observed in this sample, an inverse relation between dietary vitamin D and risk of cutaneous malignant melanoma may exist.


Further heterogeneity demonstrated for serum creatine kinase isoenzyme MM.
Serum creatine kinase (EC 184.108.40.206) isoenzyme MM was resolved by isoelectric focusing into a five-band pattern, a pattern that gradually changed after the onset of myocardial infarction. Similar changes were also demonstrated in patients undergoing coronary-bypass surgery. The evolution of two CK-MB sub-bands was studied in both cases. We found that three electrophoretic bands (CK-MM, pI 7.10; MM1, pI 6.88; MB1, pI 5.61) were predominant in patterns for sera collected during the early phase of myocardial infarction, but rapidly disappeared during the following hours, whereas bands of increased electrophoretic mobility (MM2, pI 6.70; MM3, pI 6.45; MM4, pI 6.25; MB2, pI 5.34) gradually increased. MM3 was always the major band at the end of the observation period in acute myocardial infarction (mean, 61.4% of total creatine kinase activity 36 h after the peak value for total creatine kinase in serum). The CK-MM bands were also present in the serum of patients without heart disease. Changes in the electrophoretic pattern were induced by a thermolabile factor in normal human serum, which transformed the muscular or myocardial MM and MM1 bands after their release into the blood stream.


Clinical and Radiographic Evaluation of Bar, Telescopic, and Locator Attachments for Implant-Stabilized Overdentures in Patients with Mandibular Atrophied Ridges: A Randomized Controlled Clinical Trial.
The aim of this study was to evaluate the clinical and radiographic peri-implant tissues of bar, Locator, and resilient telescopic attachments for two-implant stabilized overdentures in subjects with mandibular atrophied ridges. Ninety edentulous individuals with mandibular ridge atrophy were randomly assigned into three equal groups and received two implants in the canine areas. Mandibular overdentures were constructed and attached to implants with Dolder bar attachments (BOD), resilient telescopes (TOD), and Locators (LOD). Plaque scores, gingival scores, pocket depths, implant stability, width of keratinized mucosa, vertical bone loss, and horizontal bone loss were evaluated at the time of prosthesis delivery and 6 months and 12 months after delivery. With the exception of pocket depth and implant stability, all parameters showed a significant increase from prosthesis delivery to 6 months. BOD recorded the highest plaque scores, gingival scores, and pocket depths followed by LOD, and TOD recorded the lowest values. No significant difference in implant stability and keratinized mucosa was observed between groups. TOD and BOD recorded the highest vertical and horizontal bone losses, respectively. LOD recorded the lowest vertical and horizontal bone losses. There was no difference in implant survival rate between groups. Bar, resilient telescopic, and Locator attachments can be used successfully for two-implant stabilized overdentures in subjects with mandibular atrophied ridges after a 1-year follow-up period. Telescopic attachments were associated with improved clinical peri-implant soft tissues compared with other attachments. However, Locator attachments may be advantageous in terms of peri-implant bone preservation.


Isotopic history of seawater: the stable isotope character of the global ocean at present and in the geological past.
After the atmosphere, the ocean is the most well-mixed and homogeneous global geochemical reservoir. Both physical and biological processes generate elemental and isotope variations in seawater. Contrasting geochemical behaviors cause elements to be susceptible to different fractionation mechanisms, with their isotopes providing unique insights into the composition and evolution of the ocean over the course of geological history. Supplementing the traditional stable isotopes (H, C, O, N, S) that provide information about ocean processes and past environmental conditions, radiogenic isotope (Sr, Nd, Os, Pb, U) systems can be used as time markers, indicators of terrestrial weathering, and ocean water mass mixing. Recent instrumentation advances have made possible the measurement of natural stable isotope variations produced by both mass-dependent and mass-independent fractionation for an ever-increasing number of metal elements (e.g. Li, B, Mg, Si, Ca, V, Cr, Fe, Ni, Cu, Zn, Se, Mo, Cd, Tl, U). The major emphasis in this review is on the isotopic composition of the light elements based on a comparatively large literature. Unlike O, H and S, the stable isotopes of C, N and Si do not have a constant isotopic composition in the modern ocean. The major cations Ca, Mg, and Sr fixed in carbonate shells provide the best proxies for reconstruction of the composition of the ocean in the past. Exhibiting large isotope enrichments in ocean water, B and Li are suitable for the investigation of water/rock interactions and can act as monitors of former oceanic pH. The bioessential elements Zn, Cd, and Ni are indicators of paleoproductivity in the ocean. Characteristic isotope enrichments or depletions of the multivalent elements V, Cr, Fe, Se, Mo, and U record the past redox state of the ocean/atmosphere system. Case studies describe how isotopes have been used to define the seawater composition in the geological past.


Interplay of cadherin-mediated cell adhesion and canonical Wnt signaling.
The epithelial-mesenchymal transition is essential in both embryonic development and the progression of carcinomas. Wnt signaling and cadherin-mediated adhesion have been implicated in both processes; clarifying their role will depend on linking them to rearrangements of cellular structure and behavior. beta-Catenin is an essential molecule both in cadherin-mediated cell adhesion and in canonical Wnt signaling. Numerous experiments have shown that the loss of cadherin-mediated cell adhesion can promote beta-catenin release and signaling; this is accomplished by proteases, protein kinases and other molecules. Cadherin loss can also signal to several other regulatory pathways. Additionally, many target genes of Wnt signaling influence cadherin adhesion. The most conspicuous of these Wnt target genes encode the transcription factors Twist and Slug, which directly inhibit the E-cadherin gene promoter. Other Wnt/beta-catenin target genes encode metalloproteases or the cell adhesion molecule L1, which favor the degradation of E-cadherin. These factors provide a mechanism whereby cadherin loss and increased Wnt signaling induce epithelial-mesenchymal transition in both carcinomas and development.


Climbing Fiber-Mediated Spillover Transmission to Interneurons Is Regulated by EAAT4.
Neurotransmitter spillover is a form of communication not readily predicted by anatomic structure. In the cerebellum, glutamate spillover from climbing fibers recruits molecular layer interneurons in the absence of conventional synaptic connections. Spillover-mediated signaling is typically limited by transporters that bind and reuptake glutamate. Here, we show that patterned expression of the excitatory amino acid transporter 4 (EAAT4) in Purkinje cells regulates glutamate spillover to molecular layer interneurons. Using male and female Aldolase C-Venus knock-in mice to visualize zebrin microzones, we find larger climbing fiber-evoked spillover EPSCs in regions with low levels of EAAT4 compared with regions with high EAAT4. This difference is not explained by presynaptic glutamate release properties or postsynaptic receptor density but rather by differences in the glutamate concentration reaching receptors on interneurons. Inhibiting glutamate transport normalizes the differences between microzones, suggesting that heterogeneity in EAAT4 expression is a primary determinant of differential spillover. These results show that neuronal glutamate transporters limit extrasynaptic transmission in a non-cell-autonomous manner and provide new insight into the functional specialization of cerebellar microzones.SIGNIFICANCE STATEMENT Excitatory amino acid transporters (EAATs) help maintain the fidelity and independence of point-to-point synaptic transmission. Whereas glial transporters are critical to maintain low ambient levels of extracellular glutamate to prevent excitotoxicity, neuronal transporters have more subtle roles in shaping excitatory synaptic transmission. Here we show that the patterned expression of neuronal EAAT4 in cerebellar microzones controls glutamate spillover from cerebellar climbing fibers to nearby interneurons. These results contribute to fundamental understanding of neuronal transporter functions and specialization of cerebellar microzones.


Lack of synergistic effects of metabolic syndrome and plasma fibrinogen on coronary events and mortality in moderate CKD.
Metabolic syndrome and inflammation are interlinked in patients with moderate chronic kidney disease (CKD). We examined whether these 2 conditions exert additive or multiplicative joint effects on subsequent coronary events and death in 710 Atherosclerosis Risk in Communities Study participants with a glomerular filtration rate less than 60 mL/min/1.73 m(2) (<1.0 mL/s). From the lowest to the highest quartile of level of plasma fibrinogen (an inflammation marker), the prevalence of metabolic syndrome (39%, 46%, 47%, and 64%; P < 0.001) increased. In multivariate Cox regression models, each 100-mg/dL increase in plasma fibrinogen level was associated with a significantly increased hazard of fatal/nonfatal coronary events (hazard ratio [HR], 1.62; 95% confidence interval [CI], 1.33 to 1.98) and death (HR, 1.49; 95% CI, 1.28 to 1.74). In the same models, metabolic syndrome also was associated with coronary events (HR, 1.49; 95% CI, 1.01 to 2.20) and death (HR, 1.40; 95% CI, 1.01 to 1.94). There was no significant interaction of plasma fibrinogen and metabolic syndrome with respect to risk of both fatal/nonfatal coronary events (P = 0.79) and death (P = 0.29). However, patients without metabolic syndrome and in the lowest quartile of plasma fibrinogen levels had the lowest incidence of fatal/nonfatal coronary events or death, whereas those with metabolic syndrome and in the highest quartile of plasma fibrinogen levels had the highest incidence of these events. Inflammation is associated strongly with metabolic syndrome in patients with moderate CKD. Inflammation and metabolic syndrome have additive and not multiplicative joint effects on coronary events and death.


Effect of cessation of short-term therapy with ipratropium bromide on lung function and airway responsiveness.
Regular exposure to antimuscarinic drugs would be expected to upregulate airway muscarinic receptors and could cause a transient increase in airways obstruction if treatment was stopped or omitted. We have examined peak expiratory flow rate (PEFR) during treatment and forced expiratory flow in one second (FEV1) and airway responsiveness to three constrictor agonists (as the provocative dose of agonist causing a 20% fall in FEV1, (PD20)) following cessation of regular inhaled ipratropium bromide, in 13 subjects with mild stable asthma. Subjects inhaled placebo and ipratropium bromide, 80 microg q.i.d. for 14 days in a cross-over fashion with a 1 week run-in/wash-out period before and after each treatment period. Subjects recorded symptom scores and PEFR throughout the study, and FEV1 and PD20 to histamine, methacholine and metabisulphite were measured before and after cessation of treatment. When compared to baseline, FEV1 was lower after cessation of ipratropium than after placebo, with a significant difference 30 h after the last dose (difference 190 mL; 95% confidence interval (95% CI) 310-70 mL; p<0.02). FEV1 measured 6-10 days later, did not differ significantly. PEFR was significantly lower after cessation of ipratropium than after placebo on Day 15 (19-37 h after the last dose) (mean difference 4.6%; 95% CI 1.6-7.5%; p<0.01) but not on Day 16. There were no significant changes in PD20 histamine, methacholine and metabisulphite, symptom scores or rescue bronchodilator use after cessation of treatment. Thus, transient bronchoconstriction was found around 30 h after cessation of regular therapy with inhaled ipratropium for 2 weeks. The mechanism is unclear, as no evidence of muscarinic receptor upregulation was found. Although the changes were small and unlikely to be important for most patients, the results of this study indicate that the timing of lung function measurements relative to the last dose of ipratropium is important when interpreting the course of lung function in long-term studies.


Renal failure caused by a partly calcified aortic aneurysm in a patient with dabigatran therapy: A case report.
Abdominal aortic aneurysms (AAAs) are mostly asymptomatic. If aortic aneurysms become symptomatic, complications include peripheral embolization, acute aortic occlusion, and aortic rupture. However, there are also unusual complications caused by aortic aneurysms. An 87-old male with dabigatran therapy presented with newly developed melena and acute renal failure. Radiological imaging revealed an AAA with thrombotic and calcified deposits which affected the renal arteries. Gastrointestinal bleeding and hypercoagulation caused by renal failure which was triggered in turn due to an AAA. Adapted antihypertensive therapy and initiation of simvastatin 40mg once daily as well as antiplatelet therapy with aspirin 50 mg once daily due to patient's refusal of any aneurysm intervention. Neither bleeding event nor aneurysm rupture occurred with the adapted antihypertensive therapy, simvastatin and aspirin. Nonruptured AAAs can cause rare, unusual, and even life-threatening complications depending on their size and anatomical position.


Sensorial saturation for neonatal analgesia.
Sensorial saturation (SS) is a procedure in which touch, massage, taste, voice, smell, and sight compete with pain, producing almost complete analgesia during heel prick in neonates. SS is an apparently complex maneuvre, but when correctly explained it is easily learnt. In the present paper, we studied its feasibility, assessing whether a long training is really needed to achieve good results. We enrolled 66 consecutive babies and divided them randomly into 3 groups which received the following forms of analgesia: glucose plus sucking (A), SS performed by nurses (B), SS performed by mothers (C). We did not use perfume on the caregivers' hands, so that babies could smell the natural scent of the hands. We assessed pain level by the ABC scale. Median scores of groups A, B, and C were: 1 (0 to 6), 0 (0 to 4), and 0 (0 to 6), respectively. Mean scores were: 0.6, 0.6, and 1.7 and standard errors were 0.38, 0.22, and 0.32, respectively. Scores of groups B and C were significantly lower than that of A (P=0.03 and 0.006, respectively). No significant difference was found between values of scores of groups B and C. Even without the use of perfume on the hands, SS was effective as an analgesic maneuvre. It made no difference whether SS was performed by mothers who applied it for the first time or experienced nurses. SS is rapid to learn and any caregiver (mother, pediatrician or nurse) can effectively use it.


Microstructure of sheared monosized colloidal suspensions resulting from hydrodynamic and electrostatic interactions.
Hydrodynamic and near-particle interactions in sheared suspensions are communicated through suspension microstructure to produce a wide variety of rheological behaviors. To characterize this microstructure, the individual positions of monosized silica particles flowing through a microchannel are obtained with near simulation-level detail. The pair distribution functions of the microstructure at moderate to high Péclet number shear rates are very similar to previous numerical studies. Viscometric functions calculated based on the detailed microstructure obtained through this technique show qualitative agreement with computational results. These results elucidate the origins of shear-thickening of suspensions at high shear rates. While efforts are taken to screen electrostatic interactions to study hydrodynamic and Brownian interactions, the role of electrostatic interaction between particles is also investigated by reducing suspension ionic strength. These non-hydrodynamic electrostatic interactions result in a loss of anisotropy that generally agrees with previous findings of "soft" particle systems.


Initiation of Hippo signaling is linked to polarity rather than to cell position in the pre-implantation mouse embryo.
In the mouse embryo, asymmetric divisions during the 8-16 cell division generate two cell types, polar and apolar cells, that are allocated to outer and inner positions, respectively. This outer/inner configuration is the first sign of the formation of the first two cell lineages: trophectoderm (TE) and inner cell mass (ICM). Outer polar cells become TE and give rise to the placenta, whereas inner apolar cells become ICM and give rise to the embryo proper and yolk sac. Here, we analyze the frequency of asymmetric divisions during the 8-16 cell division and assess the relationships between cell polarity, cell and nuclear position, and Hippo signaling activation, the pathway that initiates lineage-specific gene expression in 16-cell embryos. Although the frequency of asymmetric divisions varied in each embryo, we found that more than six blastomeres divided asymmetrically in most embryos. Interestingly, many apolar cells in 16-cell embryos were located at outer positions, whereas only one or two apolar cells were located at inner positions. Live imaging analysis showed that outer apolar cells were eventually internalized by surrounding polar cells. Using isolated 8-cell blastomeres, we carefully analyzed the internalization process of apolar cells and found indications of higher cortical tension in apolar cells than in polar cells. Last, we found that apolar cells activate Hippo signaling prior to taking inner positions. Our results suggest that polar and apolar cells have intrinsic differences that establish outer/inner configuration and differentially regulate Hippo signaling to activate lineage-specific gene expression programs.


A review of bacterial biofilm control by physical strategies.
Biofilms are multicellular communities of microorganisms held together by a self-produced extracellular matrix, which contribute to hygiene problems in the food and medical fields. Both spoilage and pathogenic bacteria that grow in the complex structure of biofilm are more resistant to harsh environmental conditions and conventional antimicrobial agents. Therefore, it is important to develop eco-friendly preventive methodologies to eliminate biofilms from foods and food contact equipment. The present paper gives an overview of the current physical methods for biofilm control and removal. Current physical strategies adopted for the anti-biofilm treatment mainly focused on use of ultrasound power, electric or magnetic field, plasma, and irradiation. Furthermore, the mechanisms of anti-biofilm action and application of different physical methods are discussed. Physical strategies make it possible to combat biofilm without the use of biocidal agents. The remarkable microbiocidal properties of physical strategies are promising tools for antimicrobial applications.


Islet graft function by mixed meal tolerance testing is sustained over 4 years in young children undergoing total pancreatectomy with islet autotransplantation.
Children with intractable chronic pancreatitis may require total pancreatectomy with islet autotransplantation (TPIAT) for pain relief. The IAT reduces the severity of post- pancreatectomy diabetes. We analyzed 635 mixed meal tolerance tests (MMTT) in 134 children undergoing TPIAT to determine whether superior survival of islet grafts explains higher rates of insulin independence previously reported in young children (n = 52, age 3-11 years) versus adolescents (n = 82, age 12-18 years). For MMTT, children consumed Boost HP and we sampled C-peptide and glucose repeatedly over 2 h. The trajectory of outcomes before and after TPIAT was compared between children and adolescents using data from pre-TPIAT and 3, 6 months, 1, 2, 3, and 4 years post-TPIAT and mixed linear models with a random effect for child. Cox regression was used to analyze time outcomes (e.g., time to first off insulin). Islet mass transplanted, measured as islet equivalents (IEQ), was higher in adolescents (p = .003) but IEQ/kg was higher in young children (p < .001) because of their lower weight. AUC C-peptide in young children increased somewhat over 4 years, but was stable in adolescents (p = .0013). AUC glucose increased more in adolescents over time post-TPIAT (p = .0024). Islet function by AUC C-peptide:AUC glucose ratio was better preserved in young children (p < .001). Adolescents were less likely to wean off insulin (hazard ratio .44 [95% CI .28, .69]). These data support an advantage of young age in islet graft survival after TPIAT. The greater likelihood of insulin independence in young children may be driven by better islet survival after transplant.


Quality of referral: What information should be included in a request for diagnostic imaging when a patient is referred to a clinical radiologist?
Referral to a clinical radiologist is the prime means of communication between the referrer and the radiologist. Current Australian and New Zealand government regulations do not prescribe what clinical information should be included in a referral. This work presents a qualitative compilation of clinical radiologist opinion, relevant professional recommendations, governmental regulatory positions and prior work on diagnostic error to synthesise recommendations on what clinical information should be included in a referral. Recommended requirements on what clinical information should be included in a referral to a clinical radiologist are as follows: an unambiguous referral; identity of the patient; identity of the referrer; and sufficient clinical detail to justify performance of the diagnostic imaging examination and to confirm appropriate choice of the examination and modality. Recommended guideline on the content of clinical detail clarifies when the information provided in a referral meets these requirements. High-quality information provided in a referral allows the clinical radiologist to ensure that exposure of patients to medical radiation is justified. It also minimises the incidence of perceptual and interpretational diagnostic error. Recommended requirements and guideline on the clinical detail to be provided in a referral to a clinical radiologist have been formulated for professional debate and adoption.


Health benefits of finger millet (Eleusine coracana L.) polyphenols and dietary fiber: a review.
The growing public awareness of nutrition and health care research substantiates the potential of phytochemicals such as polyphenols and dietary fiber on their health beneficial properties. Hence, there is in need to identify newer sources of neutraceuticals and other natural and nutritional materials with the desirable functional characteristics. Finger millet (Eleusine coracana), one of the minor cereals, is known for several health benefits and some of the health benefits are attributed to its polyphenol and dietary fiber contents. It is an important staple food in India for people of low income groups. Nutritionally, its importance is well recognised because of its high content of calcium (0.38%), dietary fiber (18%) and phenolic compounds (0.3-3%). They are also recognized for their health beneficial effects, such as anti-diabetic, anti-tumerogenic, atherosclerogenic effects, antioxidant and antimicrobial properties. This review deals with the nature of polyphenols and dietary fiber of finger millet and their role with respect to the health benefits associated with millet.


Health effects of experiences of sexual violence for women with abusive partners.
We assessed the incidence of sexual violence, physical violence, physical health symptoms, gynecological symptoms, and risk behaviors for contracting an STD or HIV infection in women who had used a shelter for women with abusive partners. In addition, we investigated the relationships between sexual violence and the frequency of physical health symptoms, including specific gynecological symptoms. Results indicated that one fourth of the women interviewed had experienced sexual violence and nearly two thirds of the women had experienced physical violence in the past 6 months. The incidence of physical health symptoms, gynecological symptoms, and risk behaviors for exposure to STDs and HIV infection are presented. The correlations among sexual violence, physical violence, and experiences of physical health symptoms are also reported. This study is particularly valuable because previous research has not documented the relationship between sexual violence and physical health symptoms.


Traits associated with winter wheat grain yield in Central and West Asia.
Improved adaptation of winter wheat (Triticum aestivum L.) to drought and heat may be influenced by days to heading, plant height, biomass, canopy temperature (CT) at grain filling, and rate of senescence. This study shows that, under supplemental irrigation or rainfed conditions, days to heading and plant height together explain up to 68% of grain yield (GY) variation, and these associations were further confirmed in several locations across West and Central Asia. Days to heading can be slightly reduced below that of check line Karahan to further improve GY while avoiding the effect of late frosts. Plant height has been decreased in recent germplasm, but further reductions below that of check line Karahan could still improve GY in a wide range of environments. However, in Iranian sites, taller genotypes showed better adaptation with higher biomass and increased reserves for grain filling. Canopy temperature and rate senescence were not associated with GY. A normalized difference vegetation index, used to estimate biomass (Feekes stages 4-5), had intermediate heritability across environments and correlated positively with GY under low plant density and should be explored further as a tool for early selection.


Subcellular redistribution of DNA topoisomerase I in anaplastic astrocytoma cells treated with topotecan.
DNA topoisomerase I is the cytotoxic target for chemotherapeutic agents of the camptothecin class. The cytotoxicity of these drugs is thought to be mediated by a dose-dependent increase in topoisomerase I molecules bound to DNA, resulting in DNA damage and cell death. We observed that in SJ-G5 human anaplastic astrocytoma cells growing in culture, the maximum number of topoisomerase I-DNA complexes occurred 5-15 min after the addition of 0.25-25 microM 9-dimethylaminomethyl-10-hydroxycamptothecin (topotecan; TPT) or 5 microM 7-ethyl-10-hydroxycamptothecin (SN-38). We postulated that the decline in number of complexes seen after 15 min might be due to decreases in the amount of topoisomerase I or the redistribution of this enzyme such that it could no longer bind to DNA. To investigate these possibilities, we incubated SJ-G5 cells for 20-60 min with 0.25-5 microM TPT and analyzed the cells for amount and localization of topoisomerase I by indirect immunofluorescence staining and fluorescence digital imaging microscopy. We verified the results obtained with fluorescence digital imaging microscopy by rapid fractionation of nuclear and cytoplasmic proteins, separation of these proteins by polyacrylamide gel electrophoresis, and densitometric scanning of immunoblots. Results showed that topoisomerase I dissociated from nucleoli within 60 min after treatment with 1-5 microM TPT. A small (25%) but significant (P < 0.05) decrease in the amount of nuclear topoisomerase I was also observed during this time course. Simultaneously, the cytoplasmic content of the Mr 67,000 form of topoisomerase I increased 50-100%. Preincubation of cells with 10 microM cycloheximide for 10 min prevented the increase of topoisomerase I in the cytoplasm, indicating that the increase was due, at least in part, to de novo protein synthesis. Interestingly, chemotherapeutic agents other than camptothecins were also found to dissociate topoisomerase I from nucleoli. These agents included m-AMSA (4'-(9-acridinylamino)methanesulfon-m-anisidide), mitoxantrone, actinomycin D, and daunorubicin. Drugs such as 1-beta-D-arabinofuranosylcytosine or hydroxyurea, which have no effect on RNA synthesis, did not induce the translocation. The biological significance of the ability of camptothecins to redistribute their own drug target is under investigation.


Band 3 tyrosine kinase in avian erythrocyte plasma membrane is immunologically related to pp60c-src.
We have identified in the plasma membrane of the chicken erythrocyte a 60-kDa tyrosine-specific protein kinase immunologically related to the transforming protein pp60v-src of Rous sarcoma virus. The erythrocyte protein kinase phosphorylated heavy chains of tumor-bearing rabbit (TBR) antibodies reactive with pp60c-src at tyrosine in immune complex protein kinase assays. The kinase was identified as a 60-kDa protein by [35S]methionine labeling of erythrocytes and by autophosphorylation in immune complexes. The kinase migrated on two-dimensional gel electrophoresis with an apparent pI and molecular mass similar to pp60c-src. A plasma membrane-enriched fraction isolated from chicken red cells contained the majority of the kinase activity. The kinase was solubilized from the plasma membrane by the detergents 0.5% (wt/vol) Na-deoxycholate and 1% (vol/vol) Nonidet P-40. One molar NaCl was much less effective, indicating a strong association of the kinase with the plasma membrane. Incubation of the plasma membrane fraction with [32P]ATP resulted in tyrosine phosphorylation of the anion transport protein band 3. Band 3 phosphorylation was blocked by TBR antibodies, indicating that the kinase recognized by pp60c-src antibodies was responsible for band 3 phosphorylation. These results demonstrate that the avian erythrocyte plasma membrane contains a tightly bound tyrosine-specific protein kinase identical or closely related to pp60c-src and that this kinase is responsible for band 3 phosphorylation in vitro.


Exosomes in Severe Asthma: Update in Their Roles and Potential in Therapy.
Exosomes are nanosized vesicles and have recently been recognized as important players in cell-to-cell communication. Exosomes contain different mediators such as proteins, nucleic acids (DNA, mRNA, miRNAs, and other ncRNAs), and lipid mediators and can shuttle their exosomal content to both neighboring and distal cells. Exosomes are very effective in orchestrating immune responses in the airways and all cell types can contribute to the systemic exosome pool. Intracellular communication between the broad range of cell types within the lung is crucial in disease emphasizing the importance of exosomes. In asthma, exosomes affect the inflammatory microenvironment which ultimately determines the development or alleviation of the pathological symptoms. Recent studies in this area have provided insight into the underlying mechanisms of disease and led to interest in using exosomes as potential novel therapeutic agents.


Increasing the predictive accuracy of amyloid-β blood-borne biomarkers in Alzheimer's disease.
Diagnostic measures for Alzheimer's disease (AD) commonly rely on evaluating the levels of amyloid-β (Aβ) peptides within the cerebrospinal fluid (CSF) of affected individuals. These levels are often combined with levels of an additional non-Aβ marker to increase predictive accuracy. Recent efforts to overcome the invasive nature of CSF collection led to the observation of Aβ species within the blood cellular fraction, however, little is known of what additional biomarkers may be found in this membranous fraction. The current study aimed to undertake a discovery-based proteomic investigation of the blood cellular fraction from AD patients (n = 18) and healthy controls (HC; n = 15) using copper immobilized metal affinity capture and Surface Enhanced Laser Desorption/Ionisation Time-Of-Flight Mass Spectrometry. Three candidate biomarkers were observed which could differentiate AD patients from HC (ROC AUC > 0.8). Bivariate pairwise comparisons revealed significant correlations between these markers and measures of AD severity including; MMSE, composite memory, brain amyloid burden, and hippocampal volume. A partial least squares regression model was generated using the three candidate markers along with blood levels of Aβ. This model was able to distinguish AD from HC with high specificity (90%) and sensitivity (77%) and was able to separate individuals with mild cognitive impairment (MCI) who converted to AD from MCI non-converters. While requiring further characterization, these candidate biomarkers reaffirm the potential efficacy of blood-based investigations into neurodegenerative conditions. Furthermore, the findings indicate that the incorporation of non-amyloid markers into predictive models, function to increase the accuracy of the diagnostic potential of Aβ.


Immunochemical typing of amyloid deposits after microextraction from biopsies.
A simple procedure for identifying amyloid fibril proteins in biopsies and small tissue fragments is described. Amyloid fibrils from 21 patients with amyloid deposits (including 6 controls) were freed from soluble proteins and concentrated by a microextraction technique. The solubilized amyloid fibril proteins were then examined by immunodiffusion with antisera directed against amyloid fibril proteins (AA, A lambda, A kappa, ASc1, AF), cystatin C and beta 2-microglobulin. 9 out of 11 specimens with inconclusive immunohistochemical results, 5 other specimens, and 6 control specimens could clearly be typed with this method. Microextraction followed by immunochemical identification, therefore, can be considered an additional option for chemical amyloid classification in those cases in which immunohistochemical typing does not yield unequivocal results.


Preclinical Evaluation of 18F-RO6958948, 11C-RO6931643, and 11C-RO6924963 as Novel PET Radiotracers for Imaging Tau Aggregates in Alzheimer Disease.
Tau aggregates and amyloid-β (Aβ) plaques are key histopathologic features in Alzheimer disease (AD) and are considered targets for therapeutic intervention as well as biomarkers for diagnostic in vivo imaging agents. This article describes the preclinical in vitro and in vivo characterization of 3 novel compounds-RO6958948, RO6931643, and RO6924963-that bind specifically to tau aggregates and have the potential to become PET tracers for future human use. Methods: RO6958948, RO6931643, and RO6924963 were identified as high-affinity competitors at the 3H-T808 binding site on native tau aggregates in human late-stage AD brain tissue. Binding of tritiated compounds to brain tissue sections of AD patients and healthy controls was analyzed by macro- and microautoradiography and by costaining of tau aggregates and Aβ plaques on the same tissue section using specific antibodies. All 3 tracer candidates were radiolabeled with a PET nuclide and tested in vivo in tau-naïve baboons to assess brain uptake, distribution, clearance, and metabolism. Results:3H-RO6958948, 3H-RO6931643, and 3H-RO6924963 bound with high affinity and specificity to tau aggregates, clearly lacking affinity for concomitant Aβ plaques in human AD Braak V tissue sections. The specificity of all 3 radioligands for tau aggregates was supported, first, by binding patterns in AD sections comparable to the tau-specific radioligand 3H-T808; second, by very low nonspecific binding in brain tissue devoid of tau pathology, excluding significant radioligand binding to any other central nervous system target; and third, by macroscopic and microscopic colocalization and quantitative correlation of radioligand binding and tau antibody staining on the same tissue section. RO6958948, RO6931643, and RO6924963 were successfully radiolabeled with a PET nuclide at high specific activity, radiochemical purity, and yield. After intravenous administration of 18F-RO6958948, 11C-RO6931643, and 11C-RO6924963 to baboons, PET scans indicated good brain entry, rapid washout, and a favorable metabolism pattern. Conclusion:18F-RO6958948, 11C-RO6931643, and 11C-RO6924963 are promising PET tracers for visualization of tau aggregates in AD. Head-to-head comparison and validation of these tracer candidates in AD patients and healthy controls will be reported in due course.


Everyday Impact of Cognitive Interventions in Mild Cognitive Impairment: a Systematic Review and Meta-Analysis.
Cognitive interventions in Mild Cognitive Impairment (MCI) seek to ameliorate cognitive symptoms in the condition. Cognitive interventions may or may not generalize beyond cognitive outcomes to everyday life. This systematic review and meta-analysis sought to assess the effect of cognitive interventions compared to a control group in MCI on generalizability outcome measures [activities of daily living (ADLs), mood, quality of life (QOL), and metacognition] rather than cognitive outcomes alone. PRISMA guidelines were followed. MEDLINE and PsychInfo were utilized as data sources to locate references related to cognitive interventions in individuals with MCI. The cognitive intervention study was required to have a control or alternative treatment comparison group to be included. Thirty articles met criteria, including six computerized cognitive interventions, 14 therapist-based interventions, and 10 multimodal (i.e., cognitive intervention plus an additional intervention) studies. Small, but significant overall median effects were seen for ADLs (d = 0.23), mood (d = 0.16), and metacognitive outcomes (d = 0.30), but not for QOL (d = 0.10). Computerized studies appeared to benefit mood (depression, anxiety, and apathy) compared to controls, while therapist-based interventions and multimodal interventions had more impact on ADLs and metacognitive outcomes than control conditions. The results are encouraging that cognitive interventions in MCI may impact everyday life, but considerably more research is needed. The current review and meta-analysis is limited by our use of only PsychInfo and MEDLINE databases, our inability to read full text non-English articles, and our reliance on only published data to complete effect sizes.


Behavioral and plasma monoamine responses to high-speed railway noise stress in mice.
Studies have reported that railway noise causes stress responses. To evaluate the effects of high-speed railway (HSR) noise on behaviors and plasma monoamines. Institute of cancer research mice were exposed to previously recorded HSR noise for 53 days. The noise was arranged according to the HSR's 24-h traffic number and adjusted to a day-night equivalent continuous A-weighted sound pressure level (Ldn ) of 70 dB (A). The open field test (OFT) and the light/dark box test were applied to observe mice behaviors. High performance liquid chromatography-fluorimetric detection was performed to determine the concentrations of plasma norepinephrine (NE), dopamine (DA), serotonin (5-hydroxytryptamine, 5-HT). Data were analyzed by two-way analysis of variance using SPSS 16.0. After 53 days of noise exposure, center time and the frequency of line crossing of the exposed mice decreased significantly in the OFT compared with the control group. Meanwhile, transitions and the time spent in the lit compartment of the exposed group decreased significantly in the light/dark box test. After 40 days of HSR noise exposure, the concentrations of plasma DA of the exposed group were significantly higher than those of the control group, while the plasma NE and 5-HT concentrations showed no significant difference between the two groups. The behavioral tests indicate that 70 dB (A) HSR noise can result in anxiety-like behaviors in mice. The physiological results show that plasma DA is more sensitive to HSR noise compared with NE and 5-HT.


Genetic interaction with temperature is an important determinant of nematode longevity.
As in other poikilotherms, longevity in C. elegans varies inversely with temperature; worms are longer-lived at lower temperatures. While this observation may seem intuitive based on thermodynamics, the molecular and genetic basis for this phenomenon is not well understood. Several recent reports have argued that lifespan changes across temperatures are genetically controlled by temperature-specific gene regulation. Here, we provide data that both corroborate those studies and suggest that temperature-specific longevity is more the rule than the exception. By measuring the lifespans of worms with single modifications reported to be important for longevity at 15, 20, or 25 °C, we find that the effect of each modification on lifespan is highly dependent on temperature. Our results suggest that genetics play a major role in temperature-associated longevity and are consistent with the hypothesis that while aging in C. elegans is slowed by decreasing temperature, the major cause(s) of death may also be modified, leading to different genes and pathways becoming more or less important at different temperatures. These differential mechanisms of age-related death are not unlike what is observed in humans, where environmental conditions lead to development of different diseases of aging.


Reflex versus autoregulatory control of hindlimb blood flow during treadmill exercise in dogs.
To evaluate the competition between local autoregulation and reflex neurohumoral control of hindlimb blood flow (HLBF), the hindlimb vascular pressure-flow relationship was determined in nine dogs in response to a 10% decrease in mean arterial pressure (AP) imposed during both low (3.0 km/h, 0% grade) and high (5.5 km/h, 14% grade) intensities of treadmill exercise. HLBF was measured with a Doppler flow probe on the left external iliac artery, and AP was controlled with a gravity reservoir connected to the left carotid artery. A 10 +/- 2% reduction in AP for 25 min caused HLBF to decrease 25 +/- 2% during low-exercise intensity but only 10 +/- 2% during high-exercise intensity. The corresponding closed-loop gains (Gc) of HLBF regulation [Gc = 1 - (% delta hindlimb blood flow/% delta hindlimb perfusion pressure) were -1.6 +/- 0.4 and -0.06 +/- 0.2 during low- and high-exercise intensity, respectively. Autonomic ganglionic blockade (hexamethonium) increased the Gc during low-intensity exercise to 0.07 +/- 0.2. Antagonism of adenosine receptors (aminophylline) decreased the Gc of HLBF regulation during high-intensity exercise to -0.57 +/- 0.3. These data demonstrate that in response to an imposed decrease in AP, autonomic vasoconstriction overrides autoregulatory vasodilatory mechanisms during low-intensity exercise. HLBF regulation increases at a higher exercise intensity, in part due to adenosine, but autoregulation does not predominate over arterial pressure regulating mechanisms.


Chiral Instabilities and the Fate of Chirality Imbalance in Non-Abelian Plasmas.
We present a microscopic study of chiral plasma instabilities and axial charge transfer in non-Abelian plasmas with a strong gauge-matter coupling g^{2}N_{f}=64, by performing 3+1D real-time classical-statistical lattice simulation with dynamical fermions. We explicitly demonstrate for the first time that-unlike in an Abelian plasma-the transfer of chirality from the matter sector to the gauge fields occurs predominantly due to topological sphaleron transitions. We elaborate on the similiarities and differences of the axial charge dynamics in cold Abelian U(1) and non-Abelian SU(2) plasmas, and comment on the implications of our findings for the study of anomalous transport phenomena, such as the chiral magnetic effect in QCD matter.


Are the Duke criteria superior to the Beth Israel criteria for the diagnosis of infective endocarditis in children?
Accurate diagnosis of infective endocarditis may be difficult. The Beth Israel criteria and the newer Duke criteria assign probability to the diagnosis of infective endocarditis on the basis of the presence of common features and manifestations. We reviewed 111 cases of pediatric infective endocarditis diagnosed and treated over 19 years. Each case was classified by the two criteria, and the results were compared. Of 111 cases, 73 (66%) and 18 (16%) were classified as definite by the Duke criteria and the Beth Israel criteria, respectively. No cases were rejected by the Duke criteria, while 21 (19%) of 111 were rejected by the Beth Israel criteria. In 18 pathologically proven cases, reanalysis without pathological data showed that the Duke criteria had significantly greater sensitivity (83%) than the Beth Israel criteria (67%) (P < .03). Echocardiographic evidence was required in 22 cases for definite classification by the Duke criteria; none were rejected, however, when echocardiographic findings were ignored. Our results suggest that the Duke criteria are superior to the Beth Israel criteria for the diagnosis of pediatric infective endocarditis.


Anthralin cream as short contact therapy for psoriasis.
Anthralin is effective in the management of psoriasis. Because of frequent skin irritation, staining of skin and clothing, and patients' difficulty in using stiff paste and ointment preparations in traditional regimens, newer treatment protocols are being evaluated. We report a four-week study of twenty patients using an anthralin cream for thirty-minute short-contact therapy. Both 0.5 percent and 1.0 percent anthralin concentrations were evaluated. We found that short contact therapy with the anthralin cream preparations was effective. In four weeks it resulted in the clearing of treated areas in more than one-third of the patients, and significant improvement in an additional 35 percent. Little difference in efficacy was noted between the 0.5 percent and 1.0 percent concentrations. Most patients found the treatment regimen cosmetically acceptable and experienced minimal problems with staining and skin irritation.


Variation in meiotic recombination frequencies between allelic transgenes inserted at different sites in the Drosophila melanogaster genome.
Meiotic crossovers are distributed nonrandomly across the genome. Classic studies in Drosophila suggest that the position of a gene along a chromosome arm can affect the outcome of the recombination process, with proximity to the centromere being associated with lower crossing over. To examine this phenomenon molecularly, we developed an assay that measures meiotic crossovers and noncrossover gene conversions between allelic transgenes inserted into different genomic positions. To facilitate collecting a large number of virgin females, we developed a useful genetic system that kills males and undesired classes of females. We found that the recombination frequency at a site in the middle of the X chromosome, where crossovers are normally frequent, was similar to the frequency at the centromere-proximal end of the euchromatin, where crossovers are normally infrequent. In contrast, we recovered no recombinants--crossovers or noncrossovers--at a site on chromosome 4 and at a site toward the distal end of the X chromosome. These results suggest that local sequence or chromatin features have a stronger impact on recombination rates in this transgene assay than position along the chromosome arm.


I can be happy for you, but not all the time: A contingency model of envy and positive empathy in the workplace.
Although individuals are capable of feeling happiness for others' positive experiences, management scholars have thus far considered envy to be the sole emotional reaction of employees in response to coworkers' positive outcomes. In this article, we introduce the concept of positive empathy-the experience of happiness in response to a coworker's positive experience and the real or imagined happiness in the coworker-as an alternative response to envy and distinguish it from related concepts in the organizational literature. We develop a theoretical framework to explain the psychological processes that underlie envy and positive empathy, and identify individual and contextual contingencies that might incline employees to experience these emotions. Lastly, we discuss individual and organizational outcomes of envy and positive empathy and explain implications for management research and practice. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


Noninvasive low-level tragus stimulation attenuates inflammation and oxidative stress in acute heart failure.
Acute decompensated heart failure (ADHF) is associated with inflammation, oxidative stress, and excess sympathetic drive. It is unknown whether neuromodulation would improve inflammation and oxidative stress in acute heart failure. We, therefore, performed this proof-of-concept study to evaluate the effects of neuromodulation using noninvasive low-level tragus stimulation on inflammation and oxidative stress in ADHF. Nineteen patients with ejection fraction < 40% were randomized to neuromodulation 4 h twice daily (6-10 a.m. and 6-10 p.m.) (n = 8) or sham stimulation (n = 11) during hospital admission. All patients received standard-of-care treatment. Blood samples were collected at admission and discharge. Serum cytokines were assayed using standard immunosorbent techniques. Reactive oxygen species inducibility from cultured coronary endothelial cells exposed to patient sera was determined using a dihydrodichlorofluorescein probe test (expressed as fluorescein units). Compared to sham stimulation, neuromodulation was associated with a significant reduction of circulating serum interleukin-6 levels (-78% vs. -9%; p = 0.012). Similarly, neuromodulation led to a reduction of endothelial cell oxidative stress in the neuromodulation group (1363 units to 978 units, p = 0.003) compared to sham stimulation (1146 units to 1083 units, p = 0.094). No significant differences in heart rate, blood pressure, or renal function were noted between the two groups. In this proof-of-concept pilot study, in acute decompensated heart failure, neuromodulation was feasible and safe and was associated with a reduction in systemic inflammation and attenuation of coronary endothelial cellular oxidative stress. NCT02898181.


Exploratory burr holes.
The ability to enter the cranial cavity rapidly and effectively is a mandatory skill for those managing the head-injured patient. It may be increasingly required now that earlier computed tomography diagnosis of non-traumatic intracranial lesions is made in centres without the immediate assistance of a neurosurgeon.


Synergistic reduction of HIV-1 infectivity by 5-azacytidine and inhibitors of ribonucleotide reductase.
Although many compounds have been approved for the treatment of human immunodeficiency type-1 (HIV-1) infection, additional anti-HIV-1 drugs (particularly those belonging to new drug classes) are still needed due to issues such as long-term drug-associated toxicities, transmission of drug-resistant variants, and development of multi-class resistance. Lethal mutagenesis represents an antiviral strategy that has not yet been clinically translated for HIV-1 and is based on the use of small molecules to induce excessive levels of deleterious mutations within the viral genome. Here, we show that 5-azacytidine (5-aza-C), a ribonucleoside analog that induces the lethal mutagenesis of HIV-1, and multiple inhibitors of the enzyme ribonucleotide reductase (RNR) interact in a synergistic fashion to more effectively reduce the infectivity of HIV-1. In these drug combinations, RNR inhibitors failed to significantly inhibit the conversion of 5-aza-C to 5-aza-2'-deoxycytidine, suggesting that 5-aza-C acts primarily as a deoxyribonucleoside even in the presence of RNR inhibitors. The mechanism of antiviral synergy was further investigated for the combination of 5-aza-C and one specific RNR inhibitor, resveratrol, as this combination improved the selectivity index of 5-aza-C to the greatest extent. Antiviral synergy was found to be primarily due to the reduced accumulation of reverse transcription products rather than the enhancement of viral mutagenesis. To our knowledge, these observations represent the first demonstration of antiretroviral synergy between a ribonucleoside analog and RNR inhibitors, and encourage the development of additional ribonucleoside analogs and RNR inhibitors with improved antiretroviral activity.


Urban and rural differences in health insurance and access to care.
This study considers differences in access to health care and insurance characteristics between residents of urban and rural areas. Data were collected from a telephone survey of 10,310 randomly selected households in Minnesota. Sub-samples of 400 group-insured, individually insured, intermittently insured, and uninsured people, were asked about access to health care. Those with group or individual insurance were also asked about the costs and characteristics of their insurance policies. Rural areas had a higher proportion of uninsured and individually insured respondents than urban areas. Among those who purchased insurance through an employer, rural residents had fewer covered benefits than urban residents (5.1 vs 5.7, P < 0.01) and were more likely to have a deductible (80% versus 40%, P < 0.01). In spite of this, rural uninsured residents were more likely to have a regular source of care than urban residents (69% versus 51%, P < 0.01), and were less likely to have delayed care when they thought it was necessary (21% versus 32%, P < 0.01). These differences were confirmed by multivariate analysis. Rural residents with group insurance have higher out-of-pocket costs and fewer benefits. Uninsured rural residents may have better access to health care than their urban counterparts. Attempts to expand access to health care need to consider how the current structure of employment-based insurance creates inequities for individuals in rural areas as well as the burdens this structure may place on rural providers.


Balloon Test Occlusion with Perfusion CT Imaging Utilizing Intraarterial Contrast Injection.
Balloon Test Occlusion (BTO) is performed to evaluate the collateral flow when a permanent therapeutic occlusion of unilateral carotid artery is planned. BTO with neurological evaluation alone, however, has a rather high false negative rate. In order to improve the sensitivity, several adjunctive procedures such as induced hypotension or cerebral blood flow (CBF) measurement with various modalities have been combined. Perfusion CT (PCT) is another imaging modality that is mainly used for the diagnosis of acute stroke. In this study, we evaluate the efficacy and the safety of BTO combined with PCT in the same procedure utilizing intraarterial contrast injection from the catheter. Seven patients underwent BTO with PCT in our institution. All the procedures were performed in the angio/CT combination suite. BTO was performed in the usual fashion and when the patient passed the 30 minutes' BTO clinically, PCT was performed subsequently. Contrast material was injected from a Pig Tail catheter placed in the ascending aorta. The obtained data were transferred to a workstation and perfusion maps of CBF, cerebral blood volume (CBV), and time to peak (TTP) were generated using software. In three patients, single photon emission CT (SPECT) was also obtained with administering 99 mTc-ethyl cysteinate dimer (99 mTc-ECD) intravenously during BTO. Although all the patients had passed the BTO clinically, the CBF maps of three patients revealed significant decrease in the occluded hemisphere. There was no procedure-related morbidity. PCT using intraarterial contrast injection during BTO was performed successfully and safely. Intraarterial injection allowed us to obtain excellent time-attenuation curves by utilizing less contrast material and less radiation doze.


Interoperability with Moby 1.0--it's better than sharing your toothbrush!
The BioMoby project was initiated in 2001 from within the model organism database community. It aimed to standardize methodologies to facilitate information exchange and access to analytical resources, using a consensus driven approach. Six years later, the BioMoby development community is pleased to announce the release of the 1.0 version of the interoperability framework, registry Application Programming Interface and supporting Perl and Java code-bases. Together, these provide interoperable access to over 1400 bioinformatics resources worldwide through the BioMoby platform, and this number continues to grow. Here we highlight and discuss the features of BioMoby that make it distinct from other Semantic Web Service and interoperability initiatives, and that have been instrumental to its deployment and use by a wide community of bioinformatics service providers. The standard, client software, and supporting code libraries are all freely available at http://www.biomoby.org/.


Evaluating the impact of community-based health interventions: evidence from Brazil's Family Health Program.
This paper analyzes the direct and indirect impacts of Brazil's Family Health Program, using municipality level mortality data from the Brazilian Ministry of Health, and individual level data from the Brazilian household survey. We estimate the effects of the program on mortality and on household behavior related to child labor and schooling, employment of adults, and fertility. We find consistent effects of the program on reductions in mortality throughout the age distribution, but mainly at earlier ages. Municipalities in the poorest regions of the country benefit particularly from the program. For these regions, implementation of the program is also robustly associated with increased labor supply of adults, reduced fertility, and increased school enrollment. Evidence suggests that the Family Health Program is a highly cost-effective tool for improving health in poor areas.


An effect on the subjective sexual response in premenopausal women with sexual arousal disorder by bremelanotide (PT-141), a melanocortin receptor agonist.
Melanocortins affect multiple physiological responses, including sexual behaviors. Bremelanotide is a synthetic peptide melanocortin analog of alpha-melanocyte-stimulating hormone that is an agonist at melanocortin receptors MC3R and MC4R. To evaluate a single intranasal dose of bremelanotide for potential effects on physiological and subjective measurements of sexual arousal and desire in premenopausal women with sexual arousal disorder. Change in vaginal pulse amplitude during neutral and erotic videos after treatment with bremelanotide or placebo and subjects' perceptions of physiological and sexual response within 24 hours of treatment with bremelanotide or placebo. Eighteen premenopausal women with a primary diagnosis of female sexual arousal disorder were randomly assigned to receive a single intranasal dose of 20 mg bremelanotide or matching placebo in a double-blind manner during the first in-clinic treatment session, and the alternate medication during the second in-clinic treatment session. During each session, subjects viewed a 20-minute neutral video followed by a 20-minute sexually explicit video. Vaginal photoplethysmography was used to monitor vaginal vasocongestion and questionnaires were used to evaluate perceptions of sexual response within the following 24-hour period. More women reported moderate or high sexual desire following bremelanotide treatment vs. placebo (P = 0.0114), and a trend toward more positive responses regarding feelings of genital arousal occurred after bremelanotide compared with placebo (P = 0.0833). Among women who attempted sexual intercourse within 24 hours after treatment, significantly more were satisfied with their level of sexual arousal following bremelanotide, compared with placebo (P = 0.0256). Vaginal vasocongestion did not change significantly while viewing erotic videos following bremelanotide administration compared with placebo. This preliminary evaluation suggests the potential for bremelanotide to positively affect desire and arousal in women with female sexual arousal disorder and indicates that bremelanotide is a promising candidate for further evaluation in an at-home study.


Location of the neuroendocrine gonadotropin-releasing hormone neurons in the monkey hypothalamus by retrograde tracing and immunostaining*,**.
Abstract In order to localize neuroendocrine gonadotropin-releasing hormone (GnRH) neurons in the monkey hypothalamus, four juvenile cynomolgus macaques (one female, three males) were each given two or three microinjections (0.2 to 0.3 mul per site) of the retrograde tracer wheat germ agglutinin-apoHorseradish peroxidase-10 nm colloidal gold into the superficial, median eminence region of the infundibular stalk. Five to 15 days following surgery, the brains were fixed by perfusion and vibratomed at 40 mum in the frontal plane. Every 12th section was immunostained with rabbit anti-GnRH using the peroxidase anti-peroxidase technique with diaminobenzidine as the chromogen. Neuroendocrine GnRH neurons were easily identified in tissue sections as brown, immunostained cell bodies containing more than three distinct, dark blue, tracer-filled lysosomes. Neuronal counts from each complete series of sections were compiled by anatomical region, and the percentages of GnRH and neuroendocrine GnRH neurons determined. The highest proportion of neuroendocrine GnRH neurons (with projections to the median eminence) occurred in the ventral hypothalamic tract, especially in its medial third (71%), and in the supraoptic decussation just anterior to it. Proportions decreased moving laterally into the middle third (58%) and lateral third (25%) of the ventral hypothalamic tract. Further anterior and lateral, progressively smaller but significant neuroendocrine GnRH contributions were found in the supraoptic nucleus (57%) and lateral hypothalamus (33%), and in the medial preoptic area (26%). Although the medial preoptic area contained a greater percentage of the total GnRH-immunoreactive cell bodies (36%) than the ventral hypothalamic tract (27%), as a whole, the ventral hypothalamic tract contained 60% of the neuroendocrine GnRH neurons compared to only 25% from the medial preoptic area. Large numbers of GnRH cell bodies found in the diagonal band of Broca near the organum vasculosum of the lamina terminalis were not retrogradely labeled. GnRH neurons were not observed in the arcuate nucleus, the few in the paraventricular nucleus were not neuroendocrine, and the contribution from the periventricular zone was negligible. Our results here are the first to identify the neurons giving rise to the neuroendocrine GnRH system in juvenile monkeys. The data indicate that more GnRH neurons close to the infundibulum serve a neuroendocrine (perhaps hypophysiotropic) role than do those in more anterior areas. Furthermore, they suggest that the ventral hypothalamic tract is the most important, and perhaps most influential, neuroendocrine GnRH cell group in primates. The data substantiate the observed autonomy of the medial basal hypothalamus in controlling gonadotropin secretion and menstrual cyclicity in these animals. However, they also infer that perhaps 60% of the GnRH neurons do not project to the primate median eminence, and thus may serve other non-neuroendocrine functions.


[The clinical evaluation of quinine for the treatment of Plasmodium falciparum malaria].
Quinine was the first antimalarial drug to be employed and also the first resistance was noticed to. After 1960 quinine urged to be reintroduced in routine therapy alone or in combination. Aiming at evaluating the effectiveness of different schedules we studied 484 patients seen at the Malaria Laboratory. We used quinine alone in 126 patients, quinine plus sulfadoxine and pyrimethamine in 119 patients and quinine plus tetracycline in 239 patients. The results shown that 81% of all patients were treated with success and only 0.6% were R2. and there is no R3. We emphasize a high resistance rate to quinine either alone (23.1%) or associated to sulfadoxine and pyrimethamine (37.8%). A higher resistance rate seen with the combination might be linked to the smaller dose of quinine used in that instance. It is worth noting the high cure rate with the quinine-tetracycline association.


Involvement of cAMP in the cytoplasmic control of meiotic cell division in Xenopus laevis oocytes.
1) There is a large body of evidence for an inhibitory role for cAMP in progesterone induced meiosis in amphibian oocytes consistent with its known inhibitory activity in mammalian oocytes (5,26). It implies that the action of steroid hormones in this particular tissue is mediated by modifications of cAMP levels within the cell. 2) Bacterial toxins have proved to be useful reagents in the investigation of the regulatory role of cyclic nucleotides in the resumption of cell division in amphibian oocytes. 3) The possible involvement of cGMP in these processes needs to be further investigated.


Studies on B lymphoid tumors treated with monoclonal anti-idiotype antibodies: correlation with clinical responses.
Monoclonal anti-idiotype antibodies can be made which are exquisitely specific for B lymphocytic malignancies. We have conducted a clinical trial in which some patients' tumors regressed after infusion of such antibodies. Here, we evaluated characteristics of the antibodies, the tumors, and the patients to determine which features best correlated with the clinical response. Neither the isotype of the murine antibodies, nor their avidity were predictive of clinical outcome. The specific epitope to which the antibodies bound was characterized by immunochemical techniques. Reactivity with a heavy-light chain combinatorial determinant correlated somewhat with clinical effect. Variations in the characteristics of the individual tumors such as antigen sites per cell and ability to modulate the surface immunoglobulin were not predictive of response. In one patient with prolymphocytic leukemia the anti-idiotype antibody had a direct antiproliferative effect on tumor cells in vitro. This patient's tumor response was explainable by such a direct mechanism. In the other patients, who had lymphomas, therapeutic outcome correlated with the number of host nontumor cells infiltrating the tumor. The vast majority of these nontumor cells were mature T lymphocytes of the Leu 4, Leu 3 (T3, T4) phenotype. Thus, a preexistent host-tumor interaction seems to be important in the in vivo effect of anti-idiotype antibodies in B cell tumors.


The proteome complement of Nicotiana tabacum Bright-Yellow-2 culture cells.
The Nicotiana tabacum Bright-Yellow-2 (BY2) cell line is one of most commonly used plant suspension cell lines and offers interesting properties, such as fast growth, amenability to genetic transformation, and synchronization of cell division. To build a proteome reference map of BY2 cell proteins, we isolated the soluble proteins from N. tabacum BY2 cells at the end of the exponential growth phase and analyzed them by 2-DE and MALDI TOF-TOF. Of the 1422 spots isolated, 795 were identified with a significant score, corresponding to 532 distinct proteins.


CAM and cell fate targeting: molecular and energetic insights into cell growth and differentiation.
Evidence-based medicine is switching from the analysis of single diseases at a time toward an integrated assessment of a diseased person. Complementary and alternative medicine (CAM) offers multiple holistic approaches, including osteopathy, homeopathy, chiropractic, acupuncture, herbal and energy medicine and meditation, all potentially impacting on major human diseases. It is now becoming evident that acupuncture can modify the expression of different endorphin genes and the expression of genes encoding for crucial transcription factors in cellular homeostasis. Extremely low frequency magnetic fields have been found to prime the commitment to a myocardial lineage in mouse embryonic stem cells, suggesting that magnetic energy may direct stem cell differentiation into specific cellular phenotypes without the aid of gene transfer technologies. This finding may pave the way to novel approaches in tissue engineering and regeneration. Different ginseng extracts have been shown to modulate growth and differentiation in pluripotent cells and to exert wound-healing and antitumor effects through opposing activities on the vascular system, prompting the hypothesis that ancient compounds may be the target for new logics in cell therapy. These observations and the subtle entanglement among different CAM systems suggest that CAM modalities may deeply affect both the signaling and transcriptional level of cellular homeostasis. Such a perception holds promises for a new era in CAM, prompting reproducible documentation of biological responses to CAM-related strategies and compounds. To this end, functional genomics and proteomics and the comprehension of the cell signaling networks may substantially contribute to the development of a molecular evidence-based CAM.


Intraoperative Acute Multivessel Coronary Vasospasm in Cardiac Allograft: A Case Report.
We present a patient who developed acute intraoperative cardiac failure requiring open cardiac message immediately after uncomplicated heart transplantation. After successful resuscitation and establishment of extracorporeal membrane oxygenation, coronary angiography showed diffuse multivessel coronary vasospasm, which responded to intracoronary and IV administration of vasodilators. Cardiac function gradually improved and the patient was discharged home after a prolonged hospital course. Cardiac allograft dysfunction associated with coronary vasospasm immediately after heart transplantation has not previously been reported.


Characterization of the organic contamination pattern of a hyper-saline ecosystem by rapid screening using gas chromatography coupled to high-resolution time-of-flight mass spectrometry.
In this paper, gas chromatography coupled to high-resolution time-of-flight mass spectrometry (GC-TOF MS) has been applied to evaluate organic pollution in a hyper-saline aquatic environment. Firstly, a target screening was made for a list of 150 GC-amenable organic micro-contaminants, including PAHs, octyl/nonyl phenols, PCBs, PBDEs, and a notable number of pesticides, such us insecticides (organochlorines, organophosphorus, carbamates and pyrethroids), herbicides (triazines and chloroacetanilides), fungicides and several transformation products. This methodology was applied to brine samples, with a salt content from 112 g/L to saturation, and to samples from Artemia populations (crustacean Anostraca) collected during 1 year from three sampling stations in saltworks bodies sited in the Ebro river delta. Around 50 target contaminants, belong to chemical families included in the list of priority substances within the framework on European water policy. Additionally, a non-target analysis was performed in both types of samples with the objective of investigating the presence of other non-selected organic compounds taking advantage of the potential of GC-TOF MS (high sensitivity in full-spectrum acquisition mode, accurate mass measurements) for searching unknowns. Organophosphorus pesticides were the contaminants more frequently detected in brine samples. Other compounds usually present in urban and industrial wastewaters, like caffeine, methylparaben, butylated-hydroxytoluene and N-butylbenzenesulfonamide were also detected in brines. The herbicide simazine and the insecticide chlorpyrifos were among the contaminants detected in Artemia samples. Results of this work reveal a potential threat to vulnerable populations inhabiting the hyper-saline ecosystem. The valuable contribution of GC-TOF MS in environmental analysis, allowing the rapid screening of a large number of organic contaminants, is also demonstrated in this paper.


Genetic influence on the development of renoprival hypertension in parabiotic rats. Evidence that a humoral hypertensinogenic factor is produced in kidney tissue of hypertension-prone rats.
Rats from two strains with opposite constitutional predisposition to hypertension were joined in parabiosis and one partner was nephrectomized. The influence of genetic factors and of diet on the blood pressures of the two classes of parabionts, operated and intact, indicated that renoprival hypertension occurred with equal frequency in rats from both strains; that the development of renoprival hypertension depended on the influence from an intact S partner, or on a high salt intake, or on both. A nephrectomized S rat developing renoprival hypertension did not induce high blood pressure in its intact R partner. In this respect renoprival hypertension differs from salt and renal hypertension. The findings are interpreted to mean that the hypertensinogenic agent specific for S rats is produced by S kidneys.


A novel form of Deleted in breast cancer 1 (DBC1) lacking the N-terminal domain does not bind SIRT1 and is dynamically regulated in vivo.
The protein Deleted in Breast Cancer-1 is a regulator of several transcription factors and epigenetic regulators, including HDAC3, Rev-erb-alpha, PARP1 and SIRT1. It is well known that DBC1 regulates its targets, including SIRT1, by protein-protein interaction. However, little is known about how DBC1 biological activity is regulated. In this work, we show that in quiescent cells DBC1 is proteolytically cleaved, producing a protein (DN-DBC1) that misses the S1-like domain and no longer binds to SIRT1. DN-DBC1 is also found in vivo in mouse and human tissues. Interestingly, DN-DBC1 is cleared once quiescent cells re-enter to the cell cycle. Using a model of liver regeneration after partial hepatectomy, we found that DN-DBC1 is down-regulated in vivo during regeneration. In fact, WT mice show a decrease in SIRT1 activity during liver regeneration, coincidentally with DN-DBC1 downregulation and the appearance of full length DBC1. This effect on SIRT1 activity was not observed in DBC1 KO mice. Finally, we found that DBC1 KO mice have altered cell cycle progression and liver regeneration after partial hepatectomy, suggesting that DBC1/DN-DBC1 transitions play a role in normal cell cycle progression in vivo after cells leave quiescence. We propose that quiescent cells express DN-DBC1, which either replaces or coexist with the full-length protein, and that restoring of DBC1 is required for normal cell cycle progression in vitro and in vivo. Our results describe for the first time in vivo a naturally occurring form of DBC1, which does not bind SIRT1 and is dynamically regulated, thus contributing to redefine the knowledge about its function.


Is Human Oxoguanine Glycosylase 1 Genetic Variant Successful Even on Oral Squamous Cell Carcinoma?
Oral squamous cell carcinoma (OSCC) is one of the most widespread cancer types that arise from different sites of oral cavity and has a 5-year survival rate. This study is aimed at investigating the human oxoguanine glycosylase 1 (hOGG1)-Ser326Cys and APE-Asp148Glu polymorphisms of DNA repair genes in OSCC. We investigated the hOGG1-Ser326Cys and APE-Asp148Glu polymorphisms of DNA repair genes in the oral cavity. Genotyping was conducted using polymerase chain reaction-restriction fragment length polymorphism analysis based on 132 patients who were diagnosed as having OSCC and 160 healthy subjects. Individuals with the genotype hOGG1-Ser326Cys, Cys allele carriers, were found significantly more frequently in the patient group compared to the control group as increase in risk (p < 0.001). Furthermore, it was observed that there were significantly more individuals with the Ser allele in the control group (p < 0.001). Individuals with genotype APE-Asp148Glu were not statistically significant; however, they were still more in the control group and provided protection against the disease. Our findings showed that hOGG1-Ser326Cys Cys allele is statistically important and relevant with respect to the development of oral squamous cancer. In view of our results, further studies including expression levels are required in which hOGG1-Ser326Cys should be investigated as molecular biomarkers for the early prediction of squamous cell carcinoma.


Ancient and modern genomes unravel the evolutionary history of the rhinoceros family.
Only five species of the once-diverse Rhinocerotidae remain, making the reconstruction of their evolutionary history a challenge to biologists since Darwin. We sequenced genomes from five rhinoceros species (three extinct and two living), which we compared to existing data from the remaining three living species and a range of outgroups. We identify an early divergence between extant African and Eurasian lineages, resolving a key debate regarding the phylogeny of extant rhinoceroses. This early Miocene (∼16 million years ago [mya]) split post-dates the land bridge formation between the Afro-Arabian and Eurasian landmasses. Our analyses also show that while rhinoceros genomes in general exhibit low levels of genome-wide diversity, heterozygosity is lowest and inbreeding is highest in the modern species. These results suggest that while low genetic diversity is a long-term feature of the family, it has been particularly exacerbated recently, likely reflecting recent anthropogenic-driven population declines.


Incident herpes simplex virus type 2 infection increases the risk of subsequent episodes of bacterial vaginosis.
Herpes simplex virus type 2 (HSV-2) infected women have a higher prevalence of bacterial vaginosis (BV) compared to HSV-2-seronegative women. To explore the temporal association between these conditions, we evaluated the frequency of BV episodes before and after HSV-2 acquisition in a prospective study of 406 HSV-2/HIV-1-seronegative Kenyan women, of whom 164 acquired HSV-2. Incident HSV-2 was associated with increased likelihood of BV (adjusted OR, 1.28; 95% CI, 1.05-1.56; P = .01). Our findings strengthen the evidence for a causal link between genital HSV-2 infection and disruption of the vaginal microbiota.


Recognition of a B cell lymphoma by anti-idiotypic T cells.
Idiotypic IgM derived from a B cell lymphoma can act as a tumor-associated Ag, in that immunization with this purified protein generates an anti-idiotypic immune response that specifically suppresses tumor development. Spleens of immune mice contain T cells that proliferate in response to idiotypic IgM. However, idiotypic Ag is presented to the T cells most efficiently in its natural form at the surface of the lymphoma cells, than as soluble IgM plus presenting cells. Variant tumors that display either little or no idiotypic IgM at the cell surface, but which are otherwise indistinguishable from parental tumor, induce a weak response or fail to stimulate the T cells, respectively. Anti-idiotypic lines and clones have been derived from the splenic T cells by growth in the presence of irradiated tumor cells. Phenotypic analysis revealed that cells from both lines and clones express CD3 and CD4 Ag, but not CD8. Recognition of tumor Id, which required no added presenting cells, was inhibited by antibody against MHC class II Ag, and variably by anti-CD4. Proliferative responses were inhibited by anti-idiotypic antibodies, but also by antibodies against the constant region of the mu H chain, indicating that perturbation of the surface IgM abrogates availability of idiotypic determinants to the T cells.


Effects of sildenafil on ventricular and vascular function in heart failure with preserved ejection fraction.
Early studies showed beneficial effects of phosphodiesterase 5 inhibitors on cardiovascular function in heart failure (HF) patients, but the RELAX trial observed no improvement in exercise capacity with sildenafil treatment in subjects with HF and preserved ejection fraction. A subgroup of participants in the RELAX trial (n=48) underwent comprehensive noninvasive cardiovascular assessment before and after treatment with sildenafil or placebo in a prospective ancillary study. Left ventricular contractility was assessed by peak power index and stroke work index. Systemic arterial load was assessed by arterial elastance (Ea) and right ventricular afterload by pulmonary artery systolic pressure. Endothelial function was assessed by reactive hyperemia index after upper arm cuff occlusion. Compared with placebo (n=25), sildenafil (n=23) decreased Ea (-0.29±0.28 mm Hg/mL versus +0.02±0.29, P=0.008) and tended to improve reactive hyperemia index (+0.30±0.45 versus -0.17±0.30, P=0.054). In contrast, left ventricular contractility was reduced by 11% to 16% with sildenafil compared with placebo (ΔPWR/EDV -52±70 versus +0±40 mm Hg/s, P=0.006; ΔSW/EDV +0.3±5.8 versus -6.0±5.1 mm Hg, P=0.04). Sildenafil had no effect on pulmonary artery systolic pressure. In subjects with HF and preserved ejection fraction, sildenafil displayed opposing effects on ventricular and vascular function. We speculate that beneficial effects of phosphodiesterase 5 inhibitors in the systemic vasculature and endothelium were insufficient to improve clinical status or that the deleterious effects on left ventricular function offset any salutary vascular effects, contributing to the absence of benefit observed with sildenafil in subjects with HF and preserved ejection fraction in the RELAX trial. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00094302.


A Placebo-Controlled Crossover Trial of Gastrin-Releasing Peptide in Childhood Autism.
The aim of this study was to evaluate the efficacy, safety, and tolerability of gastrin-releasing peptide (GRP) compared with placebo in autism spectrum disorder symptoms. This is a randomized, double-blind, placebo-controlled crossover trial using GRP 160 pmol/kg for 4 consecutive days in 10 children with autism. Outcomes were measured by the Aberrant Behavior Checklist (ABC) scale. All participants were boys, aged between 4 and 9 years. There was a reduction in the scores of the ABC range and its subscales after use GRP and placebo. The reduction was more prominent with GRP, particularly in the subscale "hyperactivity and noncompliance," but there was no statistical difference between the results (P = 0.334). After a week of infusion, 5 children showed improvement of 25% or greater in the total score of the ABC scale with GRP use and 2 with placebo use; however, there was no statistical difference (P = 0.375). There were no adverse effects, changes in vital signs, or laboratory abnormalities associated with the use of GRP. The results of this study, despite the small sample size, reinforce previous data on the safety of the GRP in short-term use. There is a need for further research with other designs and a larger sample size to evaluate the efficacy and safety of GRP in children with autism.


Hemolytic disease of the newborn caused by a new deletion of the entire beta-globin cluster.
We describe a new type of gamma delta beta-thalassemia in four generations of a family of Scotch-Irish descent. The proposita presented with hemolytic disease of the newborn, which was characterized by a microcytic anemia. Initial restriction endonuclease analysis of the DNA showed no grossly abnormal patterns, but studies of polymorphic restriction sites and gene dosage revealed an extensive deletion that removed all the beta- and beta-like globin genes from the affected chromosome. In situ hybridization of chromosome preparations with radioactive beta-globin gene probes showed that only one 11p homolog contained the beta-globin gene cluster in the affected family members.


Selectivity of antidepressants: from the monoamine hypothesis of depression to the SSRI revolution and beyond.
In 2003, available pharmacotherapy for mood disorders was based almost entirely on observations from the 1950s and 1960s that agents that enhance monoamine transmitter function are effective antidepressants. Preclinical studies show that chronic administration of all effective antidepressants increases the efficiency of post-synaptic 5-HT transmission. Many antidepressants also modify nor-adrenergic function in the central nervous system. For the majority of antidepressants, these long-term changes in serotonergic and/or noradrenergic function result from direct antagonism of serotonin and/ or norepinephrine transporters (also termed "uptake sites"). Pharmacotherapy that is highly selective for one transporter over another has been demonstrated to be effective and tolerable, whereas agents that act on multiple transporters may not necessarily achieve better efficacy and may be associated with additional adverse events. Nevertheless, the rationale is in place to suggest that antidepressants that block both the serotonin and norepinephrine transporters might provide better efficacy, which can only be determined by empirical testing.


Understanding the breast cancer experience: a qualitative study of Malaysian women.
Breast cancer is the most common and leading cause of cancer mortality among Malaysian women. Despite good survival rates, the diagnosis of cancer still invokes the feeling of stress, fear and uncertainty. Because very little is known about the experiences of Malaysian women with breast cancer, a qualitative study using semi- structured interviews to explore the lived experience of newly diagnosed breast cancer. Using a purposive sampling method, 20 Malaysian women newly diagnosed with breast cancer, including Malays (n=10) and Chinese (n=10) were recruited in two main public hospitals in Kelantan. Similarities and divergence in women's experience were identified through thematic analysis of interview transcripts. Three themes emerged from the data: uncertainty experience of the illness, transition process and fatalistic view of breast cancer. In many ways, these findings were parallel with previous studies, suggesting that the experience of breast cancer is to a certain extent similar among women newly diagnosed with breast cancer. This study adds to the sparse literature concerning the experience of illness following breast cancer diagnosis among the Malays and Chinese. More importantly, this study addressed areas that were previously lacking, specifically in depth information on breast cancer experience from a developing country with a multi-ethnic population. The results of this investigation provide preliminary information to healthcare professionals on the impact of illness and cultural influence on survivorship to plan for appropriate education and supportive programme in order to meet the needs of breast cancer women more effectively.


OCT Angiography: Measurement of Retinal Macular Microvasculature with Spectralis II OCT Angiography - Reliability and Reproducibility.
The aim of the present study was to investigate the reliability of macular microvasculature measurements in normal subjects by Heidelberg Spectralis II optical coherence tomography angiography (OCT-A) in combination with a newly made software. This prospective study included 23 eyes of 23 persons from the Erlangen Glaucoma Registry (ISSN 2191-5008, CS-2011; NTC00494923). The subjects underwent a complete clinical, standardized ophthalmologic examination to rule out any eye disease. En face OCT-A imaging was done using Heidelberg Spectralis II OCT (Heidelberg, Germany). Images were recorded with a 15 × 15° angle and a lateral resolution of 5.7 µm/pixel, resulting in a retinal section of 2.9 × 2.9 mm. The Erlangen-Angio-Tool (EA-Tool) OCT-A application performed multiple segmentations, allowing analysis of the vessel density in 12 segments. The software was coded in MATLAB. Macular data on the superficial vascular plexus (SVP), intermediate capillary plexus (ICP), and deep capillary plexus (DCP) were exported into the application and analyzed separately. The EA-Tool calculated the percentage of "white area" in the "total area" of the region of interest, called vessel density. Foveolar avascular zones (FAZs) of the SVP, ICP, and DCP were calculated manually. To investigate the reproducibility of the new software, individual scans (SVP, ICP, and DCP) were analyzed twice with the EA-Tool and intraclass coefficients (ICCs) of the vessel density values were calculated. Statistical analysis was performed with SPSS version 21.0. The mean vessel density of the SVP ranged between 30.4 and 33.5, that of the ICP between 20.9 and 24.7, and that of the DCP between 23.5 and 27.6. Bland-Altman plots showed a good reliability of two consecutive scans of each sector (S1-S12) in the SVP, ICP, and DCP. Testing reproducibility, no statistically significantly different sectorial coefficients of variation of the SVP, ICP, and DCP were observed (p > 0.05). The mean FAZ area of the SVP was 0.43 ± 0.16 mm2, that of the ICP 0.28 ± 0.1 mm2, and that of the DCP 0.44 ± 0.12 mm2. Spectralis OCT II, in combination with the semiautomated vessel density software EA-Tool, showed good or even excellent ICCs in 75% of all segments of the SVP, ICP, and DCP. The ICCs for the FAZ area in the SVP, ICP, and DCP were excellent.


Heterogeneous profiles of a factor that renders neutrophils cytotoxic obtained from a concanavalin A-stimulated spleen cell culture in partial purification process.
Concanavalin A (Con A)-stimulated rat spleen cells were cultured in a serum-free conditioned medium. This culture supernatant contained a certain factor(s) that renders neutrophil cytotoxic for various tumor cells. The factor was tentatively termed neutrophil-activating factor (NAF). Rat NAF was partially purified from the serum-free culture supernatant by using ion exchange chromatography of DEAE-Sephadex A-50, gel filtration of Sephadex G-100, and affinity chromatography of Con A-Sepharose 4B. NAF activity was eluted in broad fractions by the ion exchange chromatography and the gel filtration. Moreover, on the Con A column, some NAF activities were bound to the column, but other activities passed through the column. These results showed the heterogeneity or polydispersity of NAF activity in both molecular size and charge-based separation properties. Monoclonal antibodies were produced by fusing BALB/c myeloma cells (P3-X63 Ag8.653) with spleen cells from syngeneic mice immunized with partially purified NAF (pNAF) obtained from the gel filtration. Absorbent beads which were linked with one monoclonal antibody (ANAF-10) partially absorbed NAF activity from supernatants of a Con A-stimulated spleen cell culture. Further purification of pNAF was performed with the use of affinity chromatography of ANAF-10-linked Sepharose. Through these procedures, the NAF activity was concentrated about 10,000-fold. Heterogeneity of NAF activity, however, did not disappear in even this affinity chromatography. On the other hand, 125I-labeled material of the final product migrated to one major band corresponding with an m.w. of about 20,000 as determined by SDS-PAGE analysis, and NAF activity was detected in the same band.